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1.
Cancer Immunol Immunother ; 73(6): 113, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38693312

ABSTRACT

Senescent cells have a profound impact on the surrounding microenvironment through the secretion of numerous bioactive molecules and inflammatory factors. The induction of therapy-induced senescence by anticancer drugs is known, but how senescent tumor cells influence the tumor immune landscape, particularly neutrophil activity, is still unclear. In this study, we investigate the induction of cellular senescence in breast cancer cells and the subsequent immunomodulatory effects on neutrophils using the CDK4/6 inhibitor palbociclib, which is approved for the treatment of breast cancer and is under intense investigation for additional malignancies. Our research demonstrates that palbociclib induces a reversible form of senescence endowed with an inflammatory secretome capable of recruiting and activating neutrophils, in part through the action of interleukin-8 and acute-phase serum amyloid A1. The activation of neutrophils is accompanied by the release of neutrophil extracellular trap and the phagocytic removal of senescent tumor cells. These findings may be relevant for the success of cancer therapy as neutrophils, and neutrophil-driven inflammation can differently affect tumor progression. Our results reveal that neutrophils, as already demonstrated for macrophages and natural killer cells, can be recruited and engaged by senescent tumor cells to participate in their clearance. Understanding the interplay between senescent cells and neutrophils may lead to innovative strategies to cope with chronic or tumor-associated inflammation.


Subject(s)
Breast Neoplasms , Cellular Senescence , Neutrophils , Piperazines , Pyridines , Humans , Piperazines/pharmacology , Pyridines/pharmacology , Cellular Senescence/drug effects , Breast Neoplasms/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , Neutrophils/metabolism , Neutrophils/immunology , Neutrophils/drug effects , Cell Line, Tumor , Neutrophil Activation/drug effects , Tumor Microenvironment/drug effects
2.
Rev Assoc Med Bras (1992) ; 70(4): e20230937, 2024.
Article in English | MEDLINE | ID: mdl-38716933

ABSTRACT

OBJECTIVE: Anticipatory nausea and vomiting are unpleasant symptoms observed before undergoing chemotherapy sessions. Less is known about the occurrence of symptoms since the advent of the new neurokinin-1 antagonist. METHODS: This prospective cohort study was performed at a single Brazilian Institution. This study included breast cancer patients who received doxorubicin and cyclophosphamide chemotherapy and an appropriate antiemetic regimen (dexamethasone 10 mg, palonosetron 0.56 mg, and netupitant 300 mg in the D1 followed by dexamethasone 10 mg 12/12 h in D2 and D4). Patients used a diary to record nausea, vomiting, and use of rescue medication in the first two cycles of treatment. The prevalence of anticipatory nausea and vomiting was assessed before chemotherapy on day 1 of C2. RESULTS: From August 4, 2020, to August 12, 2021, 60 patients were screened, and 52 patients were enrolled. The mean age was 50.8 (28-69) years, most had stage III (53.8%), and most received chemotherapy with curative intent (94%). During the first cycle, the frequency of overall nausea and vomiting was 67.31%, and that of severe nausea and vomiting (defined as grade>4 on a 10-point visual scale or use of rescue medication) was 55.77%. Ten patients had anticipatory nausea and vomiting (19.23%). The occurrence of nausea and vomiting during C1 was the only statistically significant predictor of anticipatory nausea and vomiting (OR=16, 95%CI 2.4-670.9, p=0.0003). CONCLUSION: The prevalence of anticipatory nausea is still high in the era of neurokinin-1 antagonists, and failure of antiemetic control in C1 remains the main risk factor. All efforts should be made to control chemotherapy-induced nausea or nausea and vomiting on C1 to avoid anticipatory nausea.


Subject(s)
Antiemetics , Breast Neoplasms , Nausea , Humans , Female , Breast Neoplasms/drug therapy , Middle Aged , Prospective Studies , Adult , Antiemetics/therapeutic use , Aged , Nausea/chemically induced , Prevalence , Brazil/epidemiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Doxorubicin/adverse effects , Vomiting, Anticipatory , Vomiting/chemically induced , Vomiting/epidemiology , Dexamethasone/therapeutic use , Palonosetron/therapeutic use
3.
JAMA Netw Open ; 7(5): e249548, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38717774

ABSTRACT

IMPORTANCE: Diabetes is associated with poorer prognosis of patients with breast cancer. The association between diabetes and adjuvant therapies for breast cancer remains uncertain. OBJECTIVE: To comprehensively examine the associations of preexisting diabetes with radiotherapy, chemotherapy, and endocrine therapy in low-income women with breast cancer. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included women younger than 65 years diagnosed with nonmetastatic breast cancer from 2007 through 2015, followed up through 2016, continuously enrolled in Medicaid, and identified from the linked Missouri Cancer Registry and Medicaid claims data set. Data were analyzed from January 2022 to October 2023. EXPOSURE: Preexisting diabetes. MAIN OUTCOMES AND MEASURES: Logistic regression was used to estimate odds ratios (ORs) of utilization (yes/no), timely initiation (≤90 days postsurgery), and completion of radiotherapy and chemotherapy, as well as adherence (medication possession ratio ≥80%) and persistence (<90-consecutive day gap) of endocrine therapy in the first year of treatment for women with diabetes compared with women without diabetes. Analyses were adjusted for sociodemographic and tumor factors. RESULTS: Among 3704 women undergoing definitive surgery, the mean (SD) age was 51.4 (8.6) years, 1038 (28.1%) were non-Hispanic Black, 2598 (70.1%) were non-Hispanic White, 765 (20.7%) had a diabetes history, 2369 (64.0%) received radiotherapy, 2237 (60.4%) had chemotherapy, and 2505 (67.6%) took endocrine therapy. Compared with women without diabetes, women with diabetes were less likely to utilize radiotherapy (OR, 0.67; 95% CI, 0.53-0.86), receive chemotherapy (OR, 0.67; 95% CI, 0.48-0.93), complete chemotherapy (OR, 0.71; 95% CI, 0.50-0.99), and be adherent to endocrine therapy (OR, 0.71; 95% CI, 0.56-0.91). There were no significant associations of diabetes with utilization (OR, 0.95; 95% CI, 0.71-1.28) and persistence (OR, 1.09; 95% CI, 0.88-1.36) of endocrine therapy, timely initiation of radiotherapy (OR, 1.09; 95% CI, 0.86-1.38) and chemotherapy (OR, 1.09; 95% CI, 0.77-1.55), or completion of radiotherapy (OR, 1.25; 95% CI, 0.91-1.71). CONCLUSIONS AND RELEVANCE: In this cohort study, preexisting diabetes was associated with subpar adjuvant therapies for breast cancer among low-income women. Improving diabetes management during cancer treatment is particularly important for low-income women with breast cancer who may have been disproportionately affected by diabetes and are likely to experience disparities in cancer treatment and outcomes.


Subject(s)
Breast Neoplasms , Diabetes Mellitus , Poverty , Humans , Female , Breast Neoplasms/therapy , Breast Neoplasms/epidemiology , Middle Aged , Poverty/statistics & numerical data , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Adult , United States/epidemiology , Medicaid/statistics & numerical data , Cohort Studies , Missouri/epidemiology , Chemotherapy, Adjuvant/statistics & numerical data , Medication Adherence/statistics & numerical data
4.
Cell Death Dis ; 15(5): 322, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719798

ABSTRACT

Metastatic dissemination from the primary tumor is a complex process that requires crosstalk between tumor cells and the surrounding milieu and involves the interplay between numerous cellular-signaling programs. Epithelial-mesenchymal transition (EMT) remains at the forefront of orchestrating a shift in numerous cellular programs, such as stemness, drug resistance, and apoptosis that allow for successful metastasis. Till date, there is limited success in therapeutically targeting EMT. Utilizing a high throughput screen of FDA-approved compounds, we uncovered a novel role of the topoisomerase inhibitor, Teniposide, in reversing EMT. Here, we demonstrate Teniposide as a potent modulator of the EMT program, specifically through an IRF7-NMI mediated response. Furthermore, Teniposide significantly reduces the expression of the key EMT transcriptional regulator, Zinc Finger E-Box Binding Homeobox 2 (ZEB2). ZEB2 downregulation by Teniposide inhibited RNA polymerase I (Pol I) activity and rRNA biogenesis. Importantly, Teniposide treatment markedly reduced pulmonary colonization of breast cancer cells. We have uncovered a novel role of Teniposide, which when used at a very low concentration, mitigates mesenchymal-like invasive phenotype. Overall, its ability to target EMT and rRNA biogenesis makes Teniposide a viable candidate to be repurposed as a therapeutic option to restrict breast cancer metastases.


Subject(s)
Breast Neoplasms , Down-Regulation , Epithelial-Mesenchymal Transition , RNA Polymerase I , Teniposide , Zinc Finger E-box Binding Homeobox 2 , Epithelial-Mesenchymal Transition/drug effects , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Female , Zinc Finger E-box Binding Homeobox 2/metabolism , Zinc Finger E-box Binding Homeobox 2/genetics , Cell Line, Tumor , Down-Regulation/drug effects , RNA Polymerase I/metabolism , Teniposide/pharmacology , Animals , Mice , Gene Expression Regulation, Neoplastic/drug effects
5.
J Cell Mol Med ; 28(9): e18374, 2024 May.
Article in English | MEDLINE | ID: mdl-38722288

ABSTRACT

The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.


Subject(s)
Breast Neoplasms , Organoids , Precision Medicine , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Female , Organoids/drug effects , Organoids/pathology , Organoids/metabolism , Precision Medicine/methods , Animals , Xenograft Model Antitumor Assays , Mice , Drug Resistance, Neoplasm/drug effects , Drug Screening Assays, Antitumor/methods , Middle Aged
6.
Int J Biol Sci ; 20(7): 2686-2697, 2024.
Article in English | MEDLINE | ID: mdl-38725852

ABSTRACT

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Breast cancer stem cells (BCSCs) are believed to play a crucial role in the carcinogenesis, therapy resistance, and metastasis of TNBC. It is well known that inflammation promotes stemness. Several studies have identified breast cancer-associated gene 2 (BCA2) as a potential risk factor for breast cancer incidence and prognosis. However, whether and how BCA2 promotes BCSCs has not been elucidated. Here, we demonstrated that BCA2 specifically promotes lipopolysaccharide (LPS)-induced BCSCs through LPS induced SOX9 expression. BCA2 enhances the interaction between myeloid differentiation primary response protein 88 (MyD88) and Toll-like receptor 4 (TLR4) and inhibits the interaction of MyD88 with deubiquitinase OTUD4 in the LPS-mediated NF-κB signaling pathway. And SOX9, an NF-κB target gene, mediates BCA2's pro-stemness function in TNBC. Our findings provide new insights into the molecular mechanisms by which BCA2 promotes breast cancer and potential therapeutic targets for the treatment of breast cancer.


Subject(s)
Lipopolysaccharides , Neoplastic Stem Cells , SOX9 Transcription Factor , Humans , SOX9 Transcription Factor/metabolism , SOX9 Transcription Factor/genetics , Female , Lipopolysaccharides/pharmacology , Neoplastic Stem Cells/metabolism , Cell Line, Tumor , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Myeloid Differentiation Factor 88/metabolism , Myeloid Differentiation Factor 88/genetics , NF-kappa B/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Up-Regulation , Signal Transduction , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Gene Expression Regulation, Neoplastic
7.
Int J Biol Sci ; 20(7): 2403-2421, 2024.
Article in English | MEDLINE | ID: mdl-38725848

ABSTRACT

Ciliogenesis-associated kinase 1 (CILK1) plays a key role in the ciliogenesis and ciliopathies. It remains totally unclear whether CILK1 is involved in tumor progression and therapy resistance. Here, we report that the aberrant high-expression of CILK1 in breast cancer is required for tumor cell proliferation and chemoresistance. Two compounds, CILK1-C30 and CILK1-C28, were identified with selective inhibitory effects towards the Tyr-159/Thr-157 dual-phosphorylation of CILK1, pharmacological inhibition of CILK1 significantly suppressed tumor cell proliferation and overcame chemoresistance in multiple experimental models. Large-scale screen of CILK1 substrates confirmed that the kinase directly phosphorylates ERK1, which is responsible for CILK1-mediated oncogenic function. CILK1 is also indicated to be responsible for the chemoresistance of small-cell lung cancer cells. Our data highlight the importance of CILK1 in cancer, implicating that targeting CILK1/ERK1 might offer therapeutic benefit to cancer patients.


Subject(s)
Breast Neoplasms , Cell Proliferation , Drug Resistance, Neoplasm , Humans , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Drug Resistance, Neoplasm/genetics , Female , Phosphorylation , Cell Line, Tumor , Mitogen-Activated Protein Kinase 3/metabolism , Animals , Proto-Oncogene Proteins , MAP Kinase Kinase Kinases
8.
Front Immunol ; 15: 1390261, 2024.
Article in English | MEDLINE | ID: mdl-38726001

ABSTRACT

Objective: The aim of this study was to identify the molecular subtypes of breast cancer based on chromatin regulator-related genes. Methods: The RNA sequencing data of The Cancer Genome Atlas-Breast Cancer cohort were obtained from the official website, while the single-cell data were downloaded from the Gene Expression Omnibus database (GSE176078). Validation was performed using the Molecular Taxonomy of Breast Cancer International Consortium dataset. Furthermore, the immune characteristics, tumor stemness, heterogeneity, and clinical characteristics of these molecular subtypes were analyzed. The correlation between chromatin regulators and chemotherapy resistance was examined in vitro using the quantitative real-time polymerase chain reaction (qRT-PCR) and Cell Counting Kit-8 (CCK8) assays. Results: This study identified three stable molecular subtypes with different prognostic and pathological features. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction analyses revealed that the differentially expressed genes were associated with disease processes, such as mitotic nuclear division, chromosome segregation, condensed chromosome, and specific chromosome region. The T stage and subtypes were correlated with the clinical features. Tumor heterogeneity (mutant-allele tumor heterogeneity, tumor mutational burden, purity, and homologous recombination deficiency) and tumor stemness (RNA expression-based stemness score, epigenetically regulated RNA expression-based stemness score, DNA methylation-based stemness score, and epigenetically regulated DNA methylation-based stemness score) significantly varied between the three subtypes. Furthermore, Western blotting, qRT-PCR, and CCK8 assays demonstrated that the expression of ASCL1 was positively correlated with chemotherapy resistance in breast cancer. Conclusion: This study identified the subtypes of breast cancer based on chromatin regulators and analyzed their clinical features, gene mutation status, immunophenotype, and drug sensitivity. The results of this study provide effective strategies for assessing clinical prognosis and developing personalized treatment strategies.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Breast Neoplasms , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Humans , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Drug Resistance, Neoplasm/genetics , Female , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Chromatin/genetics , Prognosis , Biomarkers, Tumor/genetics , Cell Line, Tumor , Gene Expression Profiling
9.
PLoS One ; 19(5): e0302856, 2024.
Article in English | MEDLINE | ID: mdl-38722955

ABSTRACT

Metastasis is the most dreaded outcome after a breast cancer diagnosis, and little is known regarding what triggers or promotes breast cancer to spread distally, or how to prevent or eradicate metastasis effectively. Bilateral breast cancers are an uncommon form of breast cancers. In our study, a percentage of bilateral breast cancers were clonally related based on copy number variation profiling. Whole exome sequencing and comparative sequence analysis revealed that a limited number of somatic mutations were acquired in this "breast-to-breast" metastasis that might promote breast cancer distant spread. One somatic mutation acquired was SIVA-D160N that displayed pro-metastatic phenotypes in vivo and in vitro. Over-expression of SIVA-D160N promoted migration and invasion of human MB-MDA-231 breast cancer cells in vitro, consistent with a dominant negative interfering function. When introduced via tail vein injection, 231 cells over-expressing SIVA-D160N displayed enhanced distant spread on IVIS imaging. Over-expression of SIVA-D160N promoted invasion and anchorage independent growth of mouse 4T1 breast cancer cells in vitro. When introduced orthotopically via mammary fat pad injection in syngeneic Balb/c mice, over-expression of SIVA-D160N in 4T1 cells increased orthotopically implanted mammary gland tumor growth as well as liver metastasis. Clonally related bilateral breast cancers represented a novel system to investigate metastasis and revealed a role of SIVA-D160N in breast cancer metastasis. Further characterization and understanding of SIVA function, and that of its interacting proteins, may elucidate mechanisms of breast cancer metastasis, providing clinically useful biomarkers and therapeutic targets.


Subject(s)
Breast Neoplasms , Neoplasm Metastasis , Female , Humans , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Animals , Mice , Cell Line, Tumor , Neoplasm Invasiveness , Mutation , Cell Movement/genetics , Mice, Inbred BALB C , DNA Copy Number Variations
10.
PLoS One ; 19(5): e0302600, 2024.
Article in English | MEDLINE | ID: mdl-38722960

ABSTRACT

Breast cancer is the second most common cancer diagnosed in women in the US with almost 280,000 new cases anticipated in 2023. Currently, on-site pathology for location guidance is not available during the collection of breast biopsies or during surgical intervention procedures. This shortcoming contributes to repeat biopsy and re-excision procedures, increasing the cost and patient discomfort during the cancer management process. Both procedures could benefit from on-site feedback, but current clinical on-site evaluation techniques are not commonly used on breast tissue because they are destructive and inaccurate. Ex-vivo microscopy is an emerging field aimed at creating histology-analogous images from non- or minimally-processed tissues, and is a promising tool for addressing this pain point in clinical cancer management. We investigated the ability structured illumination microscopy (SIM) to generate images from freshly-obtained breast tissues for structure identification and cancer identification at a speed compatible with potential on-site clinical implementation. We imaged 47 biopsies from patients undergoing a guided breast biopsy procedure using a customized SIM system and a dual-color fluorescent hematoxylin & eosin (H&E) analog. These biopsies had an average size of 0.92 cm2 (minimum 0.1, maximum 4.2) and had an average imaging time of 7:29 (minimum 0:22, maximum 37:44). After imaging, breast biopsies were submitted for standard histopathological processing and review. A board-certified pathologist returned a binary diagnostic accuracy of 96% when compared to diagnoses from gold-standard histology slides, and key tissue features including stroma, vessels, ducts, and lobules were identified from the resulting images.


Subject(s)
Breast Neoplasms , Humans , Breast Neoplasms/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/diagnostic imaging , Female , Breast/pathology , Breast/diagnostic imaging , Biopsy/methods , Microscopy/methods
11.
Sci Rep ; 14(1): 10632, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724585

ABSTRACT

While some clinics have adopted abbreviated neoadjuvant treatment for HER2-positive breast cancer, there remains a shortage of comprehensive clinical data to support this practice. This is a retrospective, multicenter study. A total of 142 patients were included in the study who are HER2-positive breast cancer, aged ≤ 65 years, with left ventricular ejection fraction ≥ 50%, received neoadjuvant chemotherapy and underwent surgery at 10 different oncology centers in Türkiye between October 2016 and December 2022. The treatment arms were divided into 4-6 cycles of docetaxel/trastuzumab/pertuzumab for arm A, 4 cycles of adriamycin/cyclophosphamide followed by 4 cycles of taxane/TP for arm B. There were 50 patients (35.2%) in arm A and 92 patients (64.8%) in arm B. The median follow-up of all of the patients was 19.9 months (95% CI 17.5-22.3). The 3-year DFS rates for treatment arms A and B were 90.0% and 83.8%, respectively, and the survival outcomes between the groups were similar (p = 0.34). Furthermore, the pathologic complete response rates were similar in both treatment arms, at 50.0% and 51.1%, respectively (p = 0.90). This study supports shortened neoadjuvant treatment of HER2-positive breast cancer, a common practice in some clinics.


Subject(s)
Anthracyclines , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms , Neoadjuvant Therapy , Receptor, ErbB-2 , Trastuzumab , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Female , Middle Aged , Neoadjuvant Therapy/methods , Receptor, ErbB-2/metabolism , Anthracyclines/therapeutic use , Anthracyclines/administration & dosage , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies , Trastuzumab/therapeutic use , Cyclophosphamide/therapeutic use , Cyclophosphamide/administration & dosage , Docetaxel/therapeutic use , Docetaxel/administration & dosage , Taxoids/therapeutic use , Taxoids/administration & dosage , Doxorubicin/therapeutic use , Doxorubicin/administration & dosage , Bridged-Ring Compounds/therapeutic use , Bridged-Ring Compounds/administration & dosage , Treatment Outcome , Aged , Antibodies, Monoclonal, Humanized
12.
World J Surg Oncol ; 22(1): 127, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725006

ABSTRACT

Sentinel node biopsy (SNB) is routinely performed in people with node-negative early breast cancer to assess the axilla. SNB has no proven therapeutic benefit. Nodal status information obtained from SNB helps in prognostication and can influence adjuvant systemic and locoregional treatment choices. However, the redundancy of the nodal status information is becoming increasingly apparent. The accuracy of radiological assessment of the axilla, combined with the strong influence of tumour biology on systemic and locoregional therapy requirements, has prompted many to consider alternative options for SNB. SNB contributes significantly to decreased quality of life in early breast cancer patients. Substantial improvements in workflow and cost could accrue by removing SNB from early breast cancer treatment. We review the current viewpoints and ideas for alternative options for assessing and managing a clinically negative axilla in patients with early breast cancer (EBC). Omitting SNB in selected cases or replacing SNB with a non-invasive predictive model appear to be viable options based on current literature.


Subject(s)
Axilla , Breast Neoplasms , Sentinel Lymph Node Biopsy , Humans , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Female , Sentinel Lymph Node Biopsy/methods , Prognosis , Neoplasm Staging , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymphatic Metastasis , Mastectomy/methods , Quality of Life
13.
World J Surg Oncol ; 22(1): 126, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725003

ABSTRACT

PURPOSE: This study investigated the changes in the fasting blood glucose (FBG), fasting triglyceride (FTG), and fasting total cholesterol (FTC) levels during neoadjuvant therapy (NAT) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and the association with pathologic complete response (pCR). METHODS: Relevant data from Sichuan Cancer Hospital from June 2019 to June 2022 were collected and analyzed, and FBG, FTG, and FTC were divided into baseline, change, and process groups, which were grouped to analyze the changes after receiving NAT and the association with pCR. RESULTS: In the estrogen receptor (ER)-negative subgroup, patients with low levels of FTG in the process group were more likely to achieve pCR compared to high levels, and in the progesterone receptor (PR)-negative subgroup, patients with lower FTG compared to higher FTG after receiving NAT was more likely to achieve pCR. CONCLUSIONS: Patients with HER2-positive BC undergoing NAT develop varying degrees of abnormalities (elevated or decreased) in FBG, FTG, and FTC; moreover, the status of FTG levels during NAT may predict pCR in ER-negative or PR-negative HER2-positive BC.Early monitoring and timely intervention for FTG abnormalities may enable this subset of patients to increase the likelihood of obtaining a pCR along with management of abnormal markers.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Neoadjuvant Therapy , Receptor, ErbB-2 , Humans , Female , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Receptor, ErbB-2/metabolism , Neoadjuvant Therapy/methods , Middle Aged , Prognosis , Biomarkers, Tumor/metabolism , Follow-Up Studies , Blood Glucose/analysis , Blood Glucose/metabolism , Adult , Receptors, Estrogen/metabolism , Triglycerides/blood , Triglycerides/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies , Receptors, Progesterone/metabolism , Cholesterol/metabolism , Cholesterol/blood , Aged , Pathologic Complete Response
14.
Clin Transl Med ; 14(5): e1681, 2024 May.
Article in English | MEDLINE | ID: mdl-38725048

ABSTRACT

BACKGROUND: We explored the potential novel anticancer mechanisms of 25-hydroxyvitamin D (25(OH)D), a vitamin D metabolite with antitumour effects in breast cancer. It is stable in serum and is used to assess vitamin D levels in clinical practice. Transfer RNA-derived small RNAs are small noncoding RNAs that generate various distinct biological functions, but more research is needed on their role in breast cancer. METHODS: Small RNA microarrays were used to explore the novel regulatory mechanism of 25(OH)D. High-throughput RNA-sequencing technology was used to detect transcriptome changes after 25(OH)D treatment and tRF-1-Ser knockdown. RNA pull-down and high-performance liquid chromatography-mass spectrometry/mass spectrometry were used to explore the proteins bound to tRF-1-Ser. In vitro and in vivo functional experiments were conducted to assess the influence of 25(OH)D and tRF-1-Ser on breast cancer. Semi-quantitative PCR was performed to detect alternative splicing events. Western blot assay and qPCR were used to assess protein and mRNA expression. RESULTS: The expression of tRF-1-Ser is negatively regulated by 25(OH)D. In our breast cancer (BRCA) clinical samples, we found that the expression of tRF-1-Ser was higher in cancer tissues than in paired normal tissues, and was significantly associated with tumour invasion. Moreover, tRF-1-Ser inhibits the function of MBNL1 by hindering its nuclear translocation. Functional experiments and transcriptome data revealed that the downregulation of tRF-1-Ser plays a vital role in the anticancer effect of 25(OH)D. CONCLUSIONS: In brief, our research revealed a novel anticancer mechanism of 25(OH)D, unveiled the vital function of tRF-1-Ser in BRCA progression, and suggested that tRF-1-Ser could emerge as a new therapeutic target for BRCA.


Subject(s)
Breast Neoplasms , Cell Proliferation , RNA-Binding Proteins , Vitamin D , Humans , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Female , Vitamin D/metabolism , Vitamin D/analogs & derivatives , Vitamin D/pharmacology , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Cell Proliferation/genetics , Mice , Animals
15.
Womens Health (Lond) ; 20: 17455057241250131, 2024.
Article in English | MEDLINE | ID: mdl-38725253

ABSTRACT

BACKGROUND: Breast cancer is prevalent worldwide, with disparities in screening, diagnosis, treatment outcomes, and survival. In Africa, the majority of women are diagnosed at advanced stages, affecting treatment outcomes. Screening is one of the best strategies to reduce mortality rates caused by this cancer. Yet in a resource-constrained setting, there is limited access to screening and early detection services, which are available only at a few referral hospitals. OBJECTIVES: We aimed to evaluate the prevalence and screening results of breast cancer using clinical breast examination coupled with fine needle aspiration cytology in a resource-constraint setting. DESIGN: A combined cross-sectional and cohort study. METHODS: Women at risk of developing breast cancer in the Kilimanjaro region of Tanzania were invited, through public announcements, to their primary healthcare facilities. A questionnaire was used to assess the participants' characteristics. The women received a clinical breast examination, and detectable lesions were subjected to a confirmatory fine needle aspiration cytology or an excisional biopsy. Preliminary data from this ongoing breast cancer control program were extracted and analyzed for this study. RESULTS: A total of 3577 women were screened for breast cancer; their mean age was 47 ± 7.53 years. About a third of them (1145, 32%) were practicing self-breast examination at least once a month. Of 200 (5.6%) with abnormal clinical breast examination, 18 (9%) were confirmed to be breast cancer, making the prevalence to be 0.5%. The vast majority of participants with breast cancer (13, 72.2%) had early disease stages, and infiltrating ductal carcinoma, no special type, was the most common (15, 83.3%) histopathology subtype. Hormonal receptor status determination results indicated that 11 (61.1%), 7 (38.9%), and 5 (27.8%) of the tumors overexpressed estrogen receptor, progesterone receptor, and human epidermal receptor-2, respectively. CONCLUSION: Our study demonstrates 5.6% of Tanzanian women have abnormal clinical breast examination findings, with 9% having breast cancer. Nearly three-quarters (72.2%) of breast cancer screened for early disease were detected in the early disease stages. This finding suggests that organized screening with clinical breast examination coupled with fine needle aspiration cytology, which is a simple and cost-effective screening method, has the potential to improve early detection and outcomes for breast cancer patients in a resource-constraint setting.


Subject(s)
Breast Neoplasms , Early Detection of Cancer , Humans , Female , Breast Neoplasms/pathology , Breast Neoplasms/epidemiology , Breast Neoplasms/diagnosis , Cross-Sectional Studies , Biopsy, Fine-Needle , Tanzania/epidemiology , Middle Aged , Early Detection of Cancer/methods , Adult , Cohort Studies , Physical Examination , Mass Screening/methods , Prevalence , Aged , Cytology
16.
Technol Cancer Res Treat ; 23: 15330338241241484, 2024.
Article in English | MEDLINE | ID: mdl-38725284

ABSTRACT

Introduction: Endoplasmic reticulum stress (ERS) was a response to the accumulation of unfolded proteins and plays a crucial role in the development of tumors, including processes such as tumor cell invasion, metastasis, and immune evasion. However, the specific regulatory mechanisms of ERS in breast cancer (BC) remain unclear. Methods: In this study, we analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) for breast cancer and identified 8 core genes associated with ERS: ELOVL2, IFNG, MAP2K6, MZB1, PCSK6, PCSK9, IGF2BP1, and POP1. We evaluated their individual expression, independent diagnostic, and prognostic values in breast cancer patients. A multifactorial Cox analysis established a risk prognostic model, validated with an external dataset. Additionally, we conducted a comprehensive assessment of immune infiltration and drug sensitivity for these genes. Results: The results indicate that these eight core genes play a crucial role in regulating the immune microenvironment of breast cancer (BRCA) patients. Meanwhile, an independent diagnostic model based on the expression of these eight genes shows limited independent diagnostic value, and its independent prognostic value is unsatisfactory, with the time ROC AUC values generally below 0.5. According to the results of logistic regression neural networks and risk prognosis models, when these eight genes interact synergistically, they can serve as excellent biomarkers for the diagnosis and prognosis of breast cancer patients. Furthermore, the research findings have been confirmed through qPCR experiments and validation. Conclusion: In conclusion, we explored the mechanisms of ERS in BRCA patients and identified 8 outstanding biomolecular diagnostic markers and prognostic indicators. The research results were double-validated using the GEO database and qPCR.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Endoplasmic Reticulum Stress , Gene Expression Regulation, Neoplastic , Tumor Microenvironment , Humans , Female , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Breast Neoplasms/pathology , Prognosis , Endoplasmic Reticulum Stress/genetics , Biomarkers, Tumor/genetics , Gene Expression Profiling , Computational Biology/methods , Databases, Genetic , ROC Curve , Kaplan-Meier Estimate , Transcriptome
17.
Cochrane Database Syst Rev ; 5: CD013822, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38726892

ABSTRACT

BACKGROUND: In breast cancer screening programmes, women may have discussions with a healthcare provider to help them decide whether or not they wish to join the breast cancer screening programme. This process is called shared decision-making (SDM) and involves discussions and decisions based on the evidence and the person's values and preferences. SDM is becoming a recommended approach in clinical guidelines, extending beyond decision aids. However, the overall effect of SDM in women deciding to participate in breast cancer screening remains uncertain. OBJECTIVES: To assess the effect of SDM on women's satisfaction, confidence, and knowledge when deciding whether to participate in breast cancer screening. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 8 August 2023. We also screened abstracts from two relevant conferences from 2020 to 2023. SELECTION CRITERIA: We included parallel randomised controlled trials (RCTs) and cluster-RCTs assessing interventions targeting various components of SDM. The focus was on supporting women aged 40 to 75 at average or above-average risk of breast cancer in their decision to participate in breast cancer screening. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and conducted data extraction, risk of bias assessment, and GRADE assessment of the certainty of the evidence. Review outcomes included satisfaction with the decision-making process, confidence in the decision made, knowledge of all options, adherence to the chosen option, women's involvement in SDM, woman-clinician communication, and mental health. MAIN RESULTS: We identified 19 studies with 64,215 randomised women, mostly with an average to moderate risk of breast cancer. Two studies covered all aspects of SDM; six examined shortened forms of SDM involving communication on risks and personal values; and 11 focused on enhanced communication of risk without other SDM aspects. SDM involving all components compared to control The two eligible studies did not assess satisfaction with the SDM process or confidence in the decision. Based on a single study, SDM showed uncertain effects on participant knowledge regarding the age to start screening (risk ratio (RR) 1.18, 95% confidence interval (CI) 0.61 to 2.28; 133 women; very low certainty evidence) and frequency of testing (RR 0.84, 95% CI 0.68 to 1.04; 133 women; very low certainty evidence). Other review outcomes were not measured. Abbreviated forms of SDM with clarification of values and preferences compared to control Of the six included studies, none evaluated satisfaction with the SDM process. These interventions may reduce conflict in the decision made, based on two measures, Decisional Conflict Scale scores (mean difference (MD) -1.60, 95% CI -4.21 to 0.87; conflict scale from 0 to 100; 4 studies; 1714 women; very low certainty evidence) and the proportion of women with residual conflict compared to control at one to three months' follow-up (rate of women with a conflicted decision, RR 0.75, 95% CI 0.56 to 0.99; 1 study; 1001 women, very low certainty evidence). Knowledge of all options was assessed through knowledge scores and informed choice. The effect of SDM may enhance knowledge (MDs ranged from 0.47 to 1.44 higher scores on a scale from 0 to 10; 5 studies; 2114 women; low certainty evidence) and may lead to higher rates of informed choice (RR 1.24, 95% CI 0.95 to 1.63; 4 studies; 2449 women; low certainty evidence) compared to control at one to three months' follow-up. These interventions may result in little to no difference in anxiety (MD 0.54, 95% -0.96 to 2.14; scale from 20 to 80; 2 studies; 749 women; low certainty evidence) and the number of women with worries about cancer compared to control at four to six weeks' follow-up (RR 0.88, 95% CI 0.73 to 1.06; 1 study, 639 women; low certainty evidence). Other review outcomes were not measured. Enhanced communication about risks without other SDM aspects compared to control Of 11 studies, three did not report relevant outcomes for this review, and none assessed satisfaction with the SDM process. Confidence in the decision made was measured by decisional conflict and anticipated regret of participating in screening or not. These interventions, without addressing values and preferences, may result in lower confidence in the decision compared to regular communication strategies at two weeks' follow-up (MD 2.89, 95% CI -2.35 to 8.14; Decisional Conflict Scale from 0 to 100; 2 studies; 1191 women; low certainty evidence). They may result in higher anticipated regret if participating in screening (MD 0.28, 95% CI 0.15 to 0.41) and lower anticipated regret if not participating in screening (MD -0.28, 95% CI -0.42 to -0.14). These interventions increase knowledge (MD 1.14, 95% CI 0.61 to 1.62; scale from 0 to 10; 4 studies; 2510 women; high certainty evidence), while it is unclear if there is a higher rate of informed choice compared to regular communication strategies at two to four weeks' follow-up (RR 1.27, 95% CI 0.83 to 1.92; 2 studies; 1805 women; low certainty evidence). These interventions result in little to no difference in anxiety (MD 0.33, 95% CI -1.55 to 0.99; scale from 20 to 80) and depression (MD 0.02, 95% CI -0.41 to 0.45; scale from 0 to 21; 2 studies; 1193 women; high certainty evidence) and lower cancer worry compared to control (MD -0.17, 95% CI -0.26 to -0.08; scale from 1 to 4; 1 study; 838 women; high certainty evidence). Other review outcomes were not measured. AUTHORS' CONCLUSIONS: Studies using abbreviated forms of SDM and other forms of enhanced communications indicated improvements in knowledge and reduced decisional conflict. However, uncertainty remains about the effect of SDM on supporting women's decisions. Most studies did not evaluate outcomes considered important for this review topic, and those that did measured different concepts. High-quality randomised trials are needed to evaluate SDM in diverse cultural settings with a focus on outcomes such as women's satisfaction with choices aligned to their values.


Subject(s)
Breast Neoplasms , Decision Making, Shared , Early Detection of Cancer , Randomized Controlled Trials as Topic , Humans , Female , Breast Neoplasms/diagnosis , Breast Neoplasms/prevention & control , Middle Aged , Adult , Aged , Patient Satisfaction , Patient Participation , Mammography
18.
PLoS One ; 19(5): e0300396, 2024.
Article in English | MEDLINE | ID: mdl-38728325

ABSTRACT

For breast cancer survivors, returning to work is an important step for their personal, financial, and psycho-social recovery. Returning to work as a school counselor can be particularly challenging because of the demands of their job and stress at work. This qualitative study examines return to work among school counselors who are breast cancer survivors. In-depth, semi-structured interviews were conducted with 28 survivors of breast cancer stages I-III between the ages of 32 and 55, and up to ten years after the completion of chemotherapy. Interviews focused on the discovery of the illness, treatment period, ramifications of the diagnosis on various aspects of life, and implications for work. Using thematic analysis of the data collected, analysis of the findings revealed three key themes: 1) "Everyone is replaceable": The significance of disruptions in work continuity for school counselors who are breast cancer survivors. 2) "From Zero to a Hundred": Challenges Faced by Counselors in Returning to Work after Breast Cancer Recovery.3) "It's hard to listen to counselees' problems when I am immersed in my own crisis": How surviving breast cancer affects return to work among school counselors. Findings highlight the unique needs of these counselors and the challenges they face upon returning to work. The study discusses recommendations for school principals including training, advocacy, and awareness to support survivors and improve their return to work.


Subject(s)
Breast Neoplasms , Cancer Survivors , Counselors , Qualitative Research , Return to Work , Humans , Female , Breast Neoplasms/psychology , Return to Work/psychology , Cancer Survivors/psychology , Middle Aged , Adult , Counselors/psychology , Schools , Counseling
19.
Medicine (Baltimore) ; 103(19): e38146, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728446

ABSTRACT

Breast cancer is a prevalent ailment among women, and the inflammatory response plays a crucial role in the management and prediction of breast cancer (BRCA). However, the new subtypes based on inflammation in BRCA research are still undefined. The databases including The Cancer Genome Atlas and gene expression omnibus were utilized to gather clinical data and somatic mutation information for approximately 1069 BRCA patients. Through Consensus Clustering, novel subtypes linked to inflammation were identified. A comparative analysis was conducted on the prognosis, and immune cell infiltration, and somatic mutation of the new subtypes. Additionally, an investigation into drug therapy and immunotherapy was conducted to distinguish high-risk individuals from low-risk ones. The findings of this investigation proposed the categorization of BRCA into innovative subtypes predicated on the inflammatory response and 6 key genes were a meaningful approach. Specifically, the low-, medium-, and high-inflammation subtypes exhibited varying degrees of association with clinicopathological features, tumor microenvironment, and prognosis. Notably, the high-inflammation subtype was characterized by a strong correlation with immunosuppressive microenvironments and a higher frequency of somatic mutations, which was an indication of poorer health. This study revealed that a brand-new classification could throw new light on the effective prognosis. The integration of multiple key genes was a new characterization that could promote more immunotherapy strategies and contribute to predicting the efficacy of the chemotherapeutic drugs.


Subject(s)
Breast Neoplasms , Inflammation , Tumor Microenvironment , Humans , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Female , Inflammation/genetics , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Prognosis , Mutation , Immunotherapy/methods , Middle Aged , Biomarkers, Tumor/genetics
20.
Medicine (Baltimore) ; 103(19): e37995, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728522

ABSTRACT

Breast cancer-related lymphedema (BCRL) occurs usually on the affected side, and its cause and pathophysiology are well known. However, the cause of edema of the upper extremity on the unaffected side is barely known. It is often considered to be chemotherapy-induced general edema, and clinical evaluation is rarely performed in these patients. This study aimed to present the clinical characteristics of unilateral breast cancer patients with edema of upper extremity on the unaffected side, and to emphasize the importance of early diagnosis and medical interventions. This study retrospectively analyzed the medical records of unilateral breast cancer patients complaining edema of upper extremity on the unaffected side, from January 2020 to May 2021. Lymphoscintigraphy was used to assist in confirming the diagnosis of lymphedema, and Doppler ultrasonography or 3D computed tomography angiography were performed to differentiate vascular problems. Fourteen patients were enrolled in the study. Seven, 3, and 4 patients had edema of both upper extremities, edema of the upper extremity on the unaffected side only, and edema of all extremities, respectively. None of the 4 patients with edema of all extremities showed abnormal findings on examination. In patients with edema in the upper extremity on the unaffected side alone, lymphatic flow dysfunction was seen in 2 patients, and deep vein thrombosis (DVT) was diagnosed in 1. In patients with edema of both upper extremities, lymphatic flow dysfunction was seen in 2 patients, and DVT was diagnosed in 3. One patient had DVT and accompanying lymphatic flow dysfunction. Lymphedema and DVT were diagnosed in a number of patients with edema of the upper extremity on the unaffected side, and lymphedema can occur without direct injury to the lymphatic flow system. Therefore, clinicians should not overlook the fact that diseases that require early diagnosis and treatment can occur in patients with edema of the unaffected upper extremity.


Subject(s)
Breast Neoplasms , Upper Extremity , Humans , Female , Middle Aged , Retrospective Studies , Upper Extremity/physiopathology , Breast Neoplasms/complications , Adult , Aged , Lymphedema/etiology , Lymphedema/diagnosis , Edema/etiology , Lymphoscintigraphy/methods , Ultrasonography, Doppler/methods , Breast Cancer Lymphedema/diagnosis , Computed Tomography Angiography/methods
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